Journal of lipid researchOct 19, 2004

Selective activation of the vitamin D receptor by a bile acid derivative called lithocholic acid acetate

Circadian Biology Weekly Brief ↗PubMed ↗DOI ↗

Updated Mar 31, 2026

Abstract

LCA acetate activates the vitamin D receptor (VDR) with 30 times the potency of lithocholic acid (LCA).

LCA acetate binds directly to VDR and shows minimal activity on other receptors, FXR and PXR.
The compound effectively induces the expression of VDR target genes in intestinal cells.
In contrast to LCA, LCA acetate inhibits the proliferation of human monoblastic leukemia cells and promotes their monocytic differentiation.
Several LCA derivatives were examined for their effects on VDR activation, identifying compounds with greater potency than LCA.
A docking model for LCA acetate binding to VDR is proposed to explain its strong activity.

Simplified

The vitamin D receptor (VDR), a member of the nuclear receptor superfamily, mediates the biological actions of the active form of vitamin D, 1alpha,25-dihydroxyvitamin D(3). It regulates calcium homeostasis, immunity, cellular differentiation, and other physiological processes. Recently, VDR was found to respond to bile acids as well as other nuclear receptors, farnesoid X receptor (FXR) and pregnane X receptor (PXR). The toxic bile acid lithocholic acid (LCA) induces its metabolism through VDR interaction. To elucidate the structure-function relationship between VDR and bile acids, we examined the effect of several LCA derivatives on VDR activation and identified compounds with more potent activity than LCA. LCA acetate is the most potent of these VDR agonists. It binds directly to VDR and activates the receptor with 30 times the potency of LCA and has no or minimal activity on FXR and PXR. LCA acetate effectively induced the expression of VDR target genes in intestinal cells. Unlike LCA, LCA acetate inhibited the proliferation of human monoblastic leukemia cells and induced their monocytic differentiation. We propose a docking model for LCA acetate binding to VDR. The development of VDR agonists derived from bile acids should be useful to elucidate ligand-selective VDR functions.

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Selective activation of the vitamin D receptor by a bile acid derivative called lithocholic acid acetate

Abstract

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